The human fetus and newborn are known to experience pain sensation [Anand K J S et al, New Engl J Med 1987; 317:1321-1329; Fitzgerald M, Br Med Bull 1991;47:667-75]. However, of greater concern is that untreated pain in the newborn may adversely affect development of the central nervous system resulting in long-term physiological and psychological consequences [Taddio A et al, Lancet 1997; 349:599-603; Graham YP et al, Dev Psychopath 1999; 11:545-565; Anand K J S et al, Biol Neonate 2000; 77:69-82; Ruda M A et al, Science 2000; 289:628-630]. As a consequence, appropriate analgesic therapy is even more important in the anaesthetic management of the very young than in adults.
Nitrous oxide (N2O) has been used for clinical anaesthesia in the young and the old for more than 150 years and remains the most commonly used anaesthetic gas. N2O usage in the paediatric surgical patient is based upon the assumption that its anaesthetic and analgesic efficacy matches that seen in adults [Eger E L, Nitrous Oxide/N2O; Elsevier, New York, 1985]. However, the expectation that efficacious analgesic drugs in adults will exert the same beneficial effects in neonates has been challenged by our recent report that nitrous oxide (N2O) is ineffective in neonatal rats because the immature pain pathways cannot activate the descending inhibitory pathway in response to nociceptive stimuli [Fitzgerald M et al, Brain Res 1986;389:261-70; van Praag H, Frenk H, Dev Brain Res 1991;64:71-76]. Experiments have shown that N2O lacks antinociceptive effects against thermal [Fujinaga M et al, Anesth Analg 2000; 91:6-10] and inflammatory [Ohashi Y et al, Pain 2002; 100:7-18] stimulation in rats under 3 weeks of age. If extrapolatable to humans, this would mean that N2O is ineffective as an analgesic agent in subjects up to and including the toddler stage. A similar rationale was thought to apply to the use of xenon as an analgesic agent.
The present invention seeks to provide an analgesic agent capable of providing effective pain relief in newborn and/or fetal subjects which alleviates one or more of the above-mentioned problems.